Do minocycline and other suppressors of microglia reactivity have a future in prevention or treatment of epilepsy?

Abraham. J., Fox P.D., Condello C., Bartolini A., Koh S.:Minocycline attenuates microglia activation and blocks the longterm epileptogenic effects of early-life seizures. Neurobiology of Disease, 2012, 46: 425-430.10.1016/j.nbd.2012.02.006Search in Google Scholar

Ahmadirad N., Shojaei A., Javan M., Pourgholami M.H., Mirnajafi-Zadeh J.:Effect of minocycline on pentylenetetrazol-induced chemical kindled seizures in mice. Neurological Sciences, 2014, 35: 571–57610.1007/s10072-013-1552-0Search in Google Scholar

Aloisi F:Immune function of microglia. Glia, 2001, 36: 165–179.10.1002/glia.1106Search in Google Scholar

Beheshti Nasr S.M., Moghimi A., Mohammad-Zadeh M., Shamsizadeh A., Noorbakhsh S.M.:The effect of minocy-cline on seizures induced by amygdala kindling in rats. Seizure, 2013, 22: 670-674.10.1016/j.seizure.2013.05.005Search in Google Scholar

Benson M.J., Thomas N.K., Talwar S., Hodson M.P., Lynch J.W., Woodruff T.M. et al.:A novel anticonvulsant mechanism via inhibition of complement receptor C5ar1 in murine epilepsy models. Neurobiology of Disease, 2015, 76: 87-97.10.1016/j.nbd.2015.02.004Search in Google Scholar

Bhandare A.M., Mohammed S., Pilowsky P.M., FarnhamAntagonism of PACAP or microglia function worsens the cardiovascular consequences of kainic-acid-induced seizures in rats. Journal of Neuroscience, 2015, 35: 2191–2199.10.1523/JNEUROSCI.4058-14.2015Search in Google Scholar

Bialer M., Johannessen S.I., Levy R.H., Perucca E., Tomson T., White H.S.:Progress report on new antiepileptic drugs: A summary of the Twelfth Eilat Conference (EILATXII). Epilepsy Research, 2015, 111: 85–141.10.1016/j.eplepsyres.2015.01.001Search in Google Scholar

Boison D.:The adenosine kinase hypothesis of epileptogenesis. Progress Neurobiology, 2008, 84: 249–262.10.1016/j.pneurobio.2007.12.002Search in Google Scholar

Borges K., Gearing M., McDermott D.L., Smith A.B., Almonte A.G., Wainer B.H. et al.:Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model. Experimental Neurology, 2003, 182: 21–34.10.1016/S0014-4886(03)00086-4Search in Google Scholar

Bruun D.A., Cao Z., Inceoglu B., Vito S.T., Austin A.T., Hulsizer S. et al.:Combined treatment with diazepam and allopregnanolone reverses tetramethylenedisulfotetramine (TETS)-induced calcium dysregulation in cultured neurons and protects TETS-intoxicated mice against lethal seizures. Neuropharmacology, 2015, 95: 332–342.10.1016/j.neuropharm.2015.03.035446606425882826Search in Google Scholar

Carmignoto G., Haydon P.G.:Astrocyte calcium signaling and epilepsy. Glia, 2012, 60: 1227–1233.10.1002/glia.22318453238822389222Search in Google Scholar

Citraro R., Leo A., Marra R., De Sarro G., Russo E.:Antiepileptogenic effects of the selective COX-2 inhibitor etoricoxib, on the development of spontaneous absence seizures in WAG/Rij rats. Brain Research Bulletin, 2015, 113: 1–7.10.1016/j.brainresbull.2015.02.00425701797Search in Google Scholar

Cusick M.F., Libbey J.E., Patel D.C., Doty D.J., Fujinami R.S.:Infiltrating macrophages are key to the development of seizures following virus infection. Journal of Virology, 2013, 87: 1849–1860.10.1128/JVI.02747-12355419523236075Search in Google Scholar

Dambach H., Hinkerohe D., Prochnow N., Stienen M.N., Moinfar Z., Haase C.G. et al.:Glia and epilepsy: experimental investigation of antiepileptic drugs in an astroglia/microglia co-culture model of inflammation. Epilepsia, 2014, 55: 184–192.10.1111/epi.1247324299259Search in Google Scholar

Eid T., Williamson A., Lee T.S., Petroff O.A., de Lanerolle N. C.:Glutamate and astrocytes-key players in human mesial temporal lobe epilepsy? Epilepsia, 2008, 49 (Suppl. 2): 42–52.10.1111/j.1528-1167.2008.01492.x18226171Search in Google Scholar

Fabene P.F., Bramanti P., Constantin G.:The emerging role for chemokines in epilepsy. Journal of Neuroimmunology, 2010, 224: 22–27.10.1016/j.jneuroim.2010.05.01620542576Search in Google Scholar

Fabene P.F., Navarro Mora G., Martinello M., Rossi B., Merigo F., Ottoboni L. et al.:A role for leukocyte-endothelial adhesion mechanisms in epilepsy. Nature Medicine, 2008, 14: 1377–1383.10.1038/nm.1878271031119029985Search in Google Scholar

Fang Z., Yang Y., Chen X., Zhang W., Xie Y., Chen Y. et al.:Advances in Autoimmune Epilepsy Associated with Antibodies, Their Potential Pathogenic Molecular Mechanisms, and Current Recommended Immunotherapies. Front. Immunol., 2017, 8: 395.10.3389/fimmu.2017.00395540390028487693Search in Google Scholar

Ginhoux F., Greter M., Leboeuf M., Nandi S., See P., Gokhan S. et al.:Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science, 2010, 330: 841–845.10.1126/science.1194637371918120966214Search in Google Scholar

Glushakov A.V., Glushakova O.Y., Doré S., Carney P.R., Hayes R.L.:Animal Models of Posttraumatic Seizures and Epilepsy. Methods in Molecular Biology, 2016, 1462: 481–519.10.1007/978-1-4939-3816-2_27603690527604735Search in Google Scholar

Haberlandt E., Weger C., Sigl S.B., Rauchenzauner M., Scholl-Bürgi S., Rostásy K. et al.:Adrenocorticotropic hormone versus pulsatile dexamethasone in the treatment of infantile epilepsy syndromes. Pediatr. Neurol., 2010, 42: 21–27.10.1016/j.pediatrneurol.2009.07.01120004858Search in Google Scholar

Heinemann U., Gabriel S., Schuchmann S., Eder C.:Contribution of astrocytes to seizure activity. Advances in Neurology, 1999, 79: 583–590.Search in Google Scholar

Heinemann U., Kaufer D., Friedman A.:Blood-brain barrier dysfunction, TGFβ signaling, and astrocyte dysfunction in epilepsy. Glia, 2012, 60: 1251–1257.10.1002/glia.22311361524822378298Search in Google Scholar

Héja L., Nyitrai G., Kékesi O., Dobolyi A., Szabó P., Fiáth R. et al.:Astrocytes convert network excitation to tonic inhibition of neurons. BMC Biology, 2012, 10: 26. doi: 10.1186/1741-7007-10-26.10.1186/1741-7007-10-26334213722420899Search in Google Scholar

Heo K., Cho Y.J., Cho K.J., Kim H.W., Kim H.J., Shin H.Y. et al.:Minocycline inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after treatment with kainic acid in mice. Neuroscience Letters, 2006, 398: 195–200.10.1016/j.neulet.2006.01.02716469440Search in Google Scholar

Holtman L., van Vliet E.A., van Schaik R., Queiroz C.M., Aronica E., Gorter J.A.:Effects of SC58236, a selective COX-2 inhibitor, on epileptogenesis and spontaneous seizures in a rat model for temporal lobe epilepsy. Epilepsy Research, 2009, 84: 56–66.10.1016/j.eplepsyres.2008.12.00619186029Search in Google Scholar

Jakubs K., Nanobashvili A., Bonde S., Ekdahl C.T., Kokaia Z., Kokaia M. et al.:Environment matters: synaptic properties of neurons born in the epileptic adult brain develop to reduce excitability. Neuron, 2006, 52: 1047–1059.10.1016/j.neuron.2006.11.00417178407Search in Google Scholar

Jessberger S., Zhao C., Toni N., Clemenson G.D. Jr, Li Y., Gage F.H.:Seizure-associated, aberrant neurogenesis in adult rats characterized with retrovirus-mediated cell labeling. Journal of Neuroscience, 2007, 27: 9400–9407.10.1523/JNEUROSCI.2002-07.2007667312817728453Search in Google Scholar

Jiang J., Quan Y., Ganesh T., Pouliot W.A., Dudek F.E., Dingledine R.:Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation. Proceedings of the National Academy of Sciences USA, 2013, 110: 3591–3596.10.1073/pnas.1218498110358723723401547Search in Google Scholar

Johnson A.C., Tremble S.M., Chan S.L., Moseley J., LaMarca B., Nagle K.J. et al.:Magnesium sulfate treatment reverses seizure susceptibility and decreases neuroinflammation in a rat model of severe preeclampsia. PLoS One, 2014, 9: e113670.10.1371/journal.pone.0113670423750225409522Search in Google Scholar

Jung K.H., Chu K., Kim M., Jeong S.W., Song Y.M., Lee S.T. et al:Continuous cytosine-b-D-arabinofuranoside infusion reduces ectopic granule cells in adult rat hippocampus with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus. European Journal of Neuroscience, 2004, 19: 3219–3226.10.1111/j.0953-816X.2004.03412.x15217378Search in Google Scholar

Jung K.H., Chu K., Lee S.T., Kim J., Sinn D.I., Kim J.M. et al.:Cyclooxygenase-2 inhibitor, celecoxib, inhibits the altered hippocampal neurogenesis with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus. Neurobiology of Disease, 2006, 23: 237–246.10.1016/j.nbd.2006.02.01616806953Search in Google Scholar

Kron M.M., Zhang H., Parent J.M.:The developmental stage of dentate granule cells dictates their contribution to seizure-inducedplasticity. Journal of Neuroscience, 2010, 30: 2051–2059.10.1523/JNEUROSCI.5655-09.2010663401520147533Search in Google Scholar

Kwon Y.S., Pineda E., Auvin S., Shin D., Mazarati A., Sankar R.:Neuroprotective and antiepileptogenic effects of combination of anti-inflammatory drugs in the immature brain. Journal of Neuroinflammation, 2013, 10: 30.10.1186/1742-2094-10-30359974923442201Search in Google Scholar

Lang N., Rothkegel H., Terney D., Antal A., Paulus W.:Minocycline exerts acute inhibitory effects on cerebral cortex excitability in humans. Epilepsy Research, 2013, 107: 302–305.10.1016/j.eplepsyres.2013.09.00624139854Search in Google Scholar

Lee D.J., Hsu M.S., Seldin M.M., Arellano J.L., Binder D.K.:Decreased expression of the glial water channel aquaporin-4 in the intrahippocampal kainic acid model of epileptogenesis. Experimental Neurology, 2012, 235: 246–255.10.1016/j.expneurol.2012.02.002333441122361023Search in Google Scholar

Legido A., Katsetos C.D.:Experimental studies in epilepsy: immunologic and inflammatory mechanisms. Seminars in Pediatric Neurology, 2014, 21: 197–206.10.1016/j.spen.2014.10.00125510941Search in Google Scholar

Li X., Han X., Yang J., Bao J., Di X., Zhang G. et al.:Magnesium Sulfate Provides Neuroprotection in Eclampsia-Like Seizure Model by Ameliorating Neuroinflammation and Brain Edema. Molecular Neurobiology, 2016. doi.org/10.1007/s12035-016-0278-4.10.1007/s12035-016-0278-427878553Search in Google Scholar

Li T., Ren G., Lusardi T., Wilz A., Lan J.Q., Iwasato T. et al.:Adenosine kinase is a target for the prediction and prevention of epileptogenesis in mice. J. Clin. Invest., 2008, 118: 571–582.10.1172/JCI33737215756818172552Search in Google Scholar

Libbey J.E., Kennett N.J., Wilcox K.S., White H.S., Fujinami R.S.:Interleukin-6, produced by resident cells of the central nervous system and infiltrating cells, contributes to the development of seizures following viral infection. Journal of Virology, 2011, 85: 6913–6922.10.1128/JVI.00458-11312657921543484Search in Google Scholar

Libbey J.E., Kennett N.J., Wilcox K.S., White H.S., Fujinami R.S.:Once initiated, viral encephalitis-induced seizures are consistent no matter the treatment or lack of interleukin-6. Journal of Neurovirology, 2011a, 17: 496–499.10.1007/s13365-011-0050-5325021821833798Search in Google Scholar

Libbey J.E., Kirkman N.J., Wilcox K.S., White H.S., Fujinami R.S.:Role for complement in the development of seizures following acute viral infection. Journal of Virology, 2010, 84: 6452–6460.10.1128/JVI.00422-10290326420427530Search in Google Scholar

Lorigados Pedre L., Morales Chacón L.M., Orozco Suárez S., Pavón Fuentes N., Estupiñán Díaz B., Serrano Sánchez T. et al.:Inflammatory mediators in epilepsy. Current Pharmaceutical Design, 2013, 19: 6766–6772.10.2174/138161281131938000923530510Search in Google Scholar

Lowenstein D.H.:Recent advances related to basic mechanisms of epileptogenesis. Epilepsy Res. Suppl., 1996, 11: 45–60.Search in Google Scholar

Lu X.C., Shear D.A., Graham P.B., Bridson G.W., Uttamsingh V., Chen Z. et al:Dual Therapeutic Effects of C-10068, a Dextromethorphan Derivative, Against Post-Traumatic Nonconvulsive Seizures and Neuroinflammation in a Rat Model of Penetrating Ballistic-Like Brain Injury. Journal of Neurotrauma, 2015, 32: 1621–1632.10.1089/neu.2014.3766459387525794265Search in Google Scholar

Luo C., Koyama R., Ikegaya Y.:Microglia engulf viable newborn cells in the epileptic dentate gyrus. Glia, 2016, 64: 1508– 1517.10.1002/glia.2301827301702Search in Google Scholar

Majkowski J.:Pathogenesis of epileptic focus. Pol. Tyg. Lek., 1994, 49: 54–58.Search in Google Scholar

Marchi N., Granata T., Freri E., Ciusani E., Ragona F., Puvenna V. et al.:Efficacy of anti-inflammatory therapy in a model of acute seizures and in a population of pediatric drug resistant epileptics. PLoS One, 2011, 6: e18200.10.1371/journal.pone.0018200306547521464890Search in Google Scholar

Matsuda T., Murao N., Katano Y., Juliandi B., Kohyama J., Akira S. et al:TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus. Nature Communications, 2015, 6: 6514.10.1038/ncomms7514436652925751136Search in Google Scholar

Matsuura R., Hamano S.I., Ikemoto S., Hirata Y., Suzuki K., Kikuchi K. et al.:Epilepsy with myoclonic atonic seizures and chronic cerebellar symptoms associated with antibodies against glutamate receptors N2B and D2 in serum and cerebrospinal fluid. Epileptic Disord., 2017, 19: 94–98.10.1684/epd.2017.089528246062Search in Google Scholar

Miranda H.F., Sierralta F., Jorquera V., Poblete P., Prieto J.C., Noriega V.:Antinociceptive interaction of gabapentin with minocycline in murine diabetic neuropathy. Inflammopharmacology, 2017, 25: 91–97.10.1007/s10787-017-0308-528155118Search in Google Scholar

Mishra M.K., Basu A.:Minocycline neuroprotects, reduces microglial activation, inhibits caspase 3 induction, and viral replication following Japanese encephalitis. Journal of Neurochemistry, 2008, 105: 1582–1595.10.1111/j.1471-4159.2008.05238.x18208541Search in Google Scholar

Mula M.:Investigational new drugs for focal epilepsy. Expert Opinion on Investigational Drugs, 2016, 25: 1–5.10.1517/13543784.2016.111014426535466Search in Google Scholar

Nowak M., Strzelczyk A., Reif P.S., Schorlemmer K., Bauer S., Norwood B.A. et al:Minocycline as potent anticonvulsant in a patient with astrocytoma and drug resistant epilepsy. Seizure, 2012, 21: 227–228.10.1016/j.seizure.2011.12.009Search in Google Scholar

Paolicelli R.C., Bolasco G., Pagani F., Maggi L., Scianni M.,Search in Google Scholar

Panzanelli P. et al:Synaptic pruning by microglia is necessary for normal brain development. Science, 2011, 333: 1456–1458.10.1126/science.1202529Search in Google Scholar

Parent J.M., von dem Bussche N., Lowenstein D.H.:Prolonged seizures recruit caudal subventricular zone glial progenitors into the injured hippocampus. Hippocampus, 2006, 16: 321–328.10.1002/hipo.20166Search in Google Scholar

Park K.I., Dzhala V., Saponjian Y., Staley K.J.:What Elements of the Inflammatory System Are Necessary for Epileptogenesis In Vitro?(1,2). eNeuro, 2015, 2 (2) ENEURO.0027-14.2015. doi. org/10.1523/ENEURO.0027-14.2015.10.1523/ENEURO.0027-14.2015Search in Google Scholar

Pitkänen A., Lukasiuk K.:Molecular and cellular basis of epileptogenesis in symptomatic epilepsy. Epilepsy Behavior, 2009, 14 (Suppl. 1): 16–25.10.1016/j.yebeh.2008.09.023Search in Google Scholar

Pitkänen A., Lukasiuk K.:Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurology, 2011, 10: 173–186.10.1016/S1474-4422(10)70310-0Search in Google Scholar

Polascheck N., Bankstahl M., Löscher W.:The COX-2 inhibitor parecoxib is neuroprotective but not antiepileptogenic in the pilocarpine model of temporal lobe epilepsy. Experimental Neurology, 2010, 224: 219–233.10.1016/j.expneurol.2010.03.01420353773Search in Google Scholar

Rossi A.R., Angelo M.F., Villarreal A., Lukin J., Ramos A.J.:Gabapentin administration reduces reactive gliosis and neurodegeneration after pilocarpine-induced status epilepticus. PLoS One, 2013, 8: e78516.10.1371/journal.pone.0078516382674024250797Search in Google Scholar

Russmann V., Goc J., Boes K., Ongerth T., Salvamoser J.D., Siegl C. et al.:Minocycline fails to exert antiepileptogenic effects in a rat status epilepticus model. European Journal of Pharmacology, 2016, 771: 29–39.10.1016/j.ejphar.2015.12.00226681545Search in Google Scholar

Salazar A.M., Grafman J.:Post-traumatic epilepsy: clinical clues to pathogenesis and paths to prevention. Handbook of Clinical Neurology, 2015, 128: 525–538.10.1016/B978-0-444-63521-1.00033-925701905Search in Google Scholar

Sato Y., Numata-Uematsu Y., Uematsu M., Kikuchi A., Nakayama T., Kakisaka Y. et al.:Acute encephalitis with refractory, repetitive partial seizures: Pathological findings and a new therapeutic approach using tacrolimus. Brain Development, 2016, 38: 772–776.10.1016/j.braindev.2016.02.006Search in Google Scholar

Schafer D.P., Lehrman E.K., Kautzman A.G., Koyama R., Mardinly A.R., Yamasaki R. et al.:Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron, 2012, 74: 691–705.10.1016/j.neuron.2012.03.026Search in Google Scholar

Scharfman H.E., Goodman J.H., Sollas A.L.:Granule-like neurons at the hilar/CA3 border after status epilepticus and their synchrony with area CA3 pyramidal cells: functional implications of seizure-induced neurogenesis. Journal of Neuroscience, 2000, 20: 6144–6158.10.1523/JNEUROSCI.20-16-06144.2000Search in Google Scholar

Seifert G., Steinhäuser C.:Neuron-astrocyte signaling and epilepsy. Experimental Neurology, 2013, 244: 4–10.10.1016/j.expneurol.2011.08.024Search in Google Scholar

Sierra A., Encinas J.M., Deudero J.J., Chancey J.H., Enikolopov G., Overstreet-Wadiche L.S. et al.:Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell, 2010, 7: 483–495.10.1016/j.stem.2010.08.014Search in Google Scholar

Steinhäuser C., Seifert G., Bedner P.:Astrocyte dysfunction in temporal lobe epilepsy: K+ channels and gap junction coupling. Glia, 2012, 60: 1192–1202.10.1002/glia.22313Search in Google Scholar

Stienen M.N., Haghikia A., Dambach H., Thöne J., Wiemann M., Gold R. et al.:Anti-inflammatory effects of the anticonvulsant drug levetiracetam on electrophysiological properties of astroglia are mediated via TGFβ1 regulation. British Journal of Pharmacology, 2011, 162: 491–507.10.1111/j.1476-5381.2010.01038.xSearch in Google Scholar

Tang Y., Le W.:Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases. Molecular Neurobiology, 2016, 53: 1181–1194.10.1007/s12035-014-9070-5Search in Google Scholar

van Vliet E.A., Aronica E., Gorter J.A.:Blood-brain barrier dysfunction, seizures and epilepsy. Seminars in Cell & Developmental Biology, 2015, 38: 26–34.10.1016/j.semcdb.2014.10.003Search in Google Scholar

Varadkar S., Bien C.G., Kruse C.A., Jensen F.E., Bauer J., Pardo C.A. et al.:Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances. Lancet Neurology, 2014, 13: 195–205.10.1016/S1474-4422(13)70260-6Search in Google Scholar

Vezzani A.:Anti-inflammatory drugs in epilepsy: does it impact epileptogenesis? Expert Opinion on Drug Safety, 2015, 14: 583–592.10.1517/14740338.2015.101050825645535Search in Google Scholar

Wang D.D., Englot D.J., Garcia P.A., Lawton M.T., Young W.L.:Minocycline-and tetracycline-class antibiotics are protective against partial seizures in vivo. Epilepsy Behav., 2012, 24: 314–318.10.1016/j.yebeh.2012.03.035376107822579030Search in Google Scholar

Wang C.H., Hsiao C.J., Lin Y.N., Wu J.W., Kuo Y.C., Lee C.K. et al.:Carbamazepine attenuates inducible nitric oxide synthase expression through Akt inhibition in activated microglial cells. Pharmaceutical Biology, 2014, 52: 1451–1459.10.3109/13880209.2014.89807425026355Search in Google Scholar

Wang N., Mi X., Gao B., Gu J., Wang W., Zhang Y. et al.:Minocycline inhibits brain inflammation and attenuates spontaneous recurrent seizures following pilocarpine-induced status epilepticus. Neuroscience, 2015, 287: 144–156.10.1016/j.neuroscience.2014.12.02125541249Search in Google Scholar

White H.S., Woodbury D.M., Chen C.F., Kemp J.W., Chow S.Y., Yen-Chow Y.C.:Role of glial cation and anion transport mechanisms in etiology and arrest of seizures. Advances in Neurology, 1986, 44: 695–712.Search in Google Scholar

Wyatt S.K., Witt T., Barbaro N.M., Cohen-Gadol A.A., Brewster A.L.:Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy. Experimental Neurology 2017, 295: 184–193.10.1016/j.expneurol.2017.06.00928601603Search in Google Scholar

Xie W., Cai L., Yu Y., Gao L., Xiao L., He Q. et al.:Activation of brain indoleamine 2,3-dioxygenase contributes to epilepsy-associated depressive-like behavior in rats with chronic temporal lobe epilepsy. Neuroinflammation, 2014, 11: 41.10.1186/1742-2094-11-41397585424594021Search in Google Scholar

Zhang B., Zou J., Han L., Rensing N., Wong M.:Microglial activation during epileptogenesis in a mouse model of tuberous sclerosis complex. Epilepsia, 2016, 57: 1317–1325.10.1111/epi.13429497267027263494Search in Google Scholar